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Omega-3 polyunsaturated fatty acids as adjuvant therapy of colorectal cancer.

ABSTRACT: The majority of evidence linking anti-colorectal cancer (CRC) activity with omega-3 polyunsaturated fatty acids (O3FAs) has focussed on decreased CRC risk (prevention). More recently, preclinical data and human observational studies have begun to make the case for adjuvant treatment of advanced CRC. Herein, we review latest data regarding the effect of O3FAs on post-diagnosis CRC outcomes, including mechanistic preclinical data, evidence that O3FAs have beneficial effects on efficacy and tolerability of CRC chemotherapy, and human epidemiological data linking dietary O3FA intake with CRC outcomes. We also highlight ongoing randomised controlled trials of O3FAs with CRC endpoints and discuss critical gaps in the evidence base, which include limited understanding of the effects of O3FAs on the tumour microenvironment, the host immune response to CRC, and the intestinal microbiome.

SUBMITTER: Volpato M

PROVIDER: S-EPMC6133177 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Omega-3 polyunsaturated fatty acids as adjuvant therapy of colorectal cancer.

Volpato Milene M Hull Mark A MA

Cancer metastasis reviews 20180901 2-3

The majority of evidence linking anti-colorectal cancer (CRC) activity with omega-3 polyunsaturated fatty acids (O3FAs) has focussed on decreased CRC risk (prevention). More recently, preclinical data and human observational studies have begun to make the case for adjuvant treatment of advanced CRC. Herein, we review latest data regarding the effect of O3FAs on post-diagnosis CRC outcomes, including mechanistic preclinical data, evidence that O3FAs have beneficial effects on efficacy and tolerab ...[more]

PMID: 29971573

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Project description:Background: Results from epidemiologic studies examining polyunsaturated fatty acids (PUFA) and colorectal cancer risk are inconsistent. Mendelian randomization may strengthen causal inference from observational studies. Given their shared metabolic pathway, examining the combined effects of aspirin/NSAID use with PUFAs could help elucidate an association between PUFAs and colorectal cancer risk.Methods: Information was leveraged from genome-wide association studies (GWAS) regarding PUFA-associated SNPs to create weighted genetic scores (wGS) representing genetically predicted circulating blood PUFAs for 11,016 non-Hispanic white colorectal cancer cases and 13,732 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations per SD increase in the wGS were estimated using unconditional logistic regression. Interactions between PUFA wGSs and aspirin/NSAID use on colorectal cancer risk were also examined.Results: Modest colorectal cancer risk reductions were observed per SD increase in circulating linoleic acid [ORLA = 0.96; 95% confidence interval (CI) = 0.93-0.98; P = 5.2 × 10-4] and ?-linolenic acid (ORALA = 0.95; 95% CI = 0.92-0.97; P = 5.4 × 10-5), whereas modest increased risks were observed for arachidonic (ORAA = 1.06; 95% CI = 1.03-1.08; P = 3.3 × 10-5), eicosapentaenoic (OREPA = 1.04; 95% CI = 1.01-1.07; P = 2.5 × 10-3), and docosapentaenoic acids (ORDPA = 1.03; 95% CI = 1.01-1.06; P = 1.2 × 10-2). Each of these effects was stronger among aspirin/NSAID nonusers in the stratified analyses.Conclusions: Our study suggests that higher circulating shorter-chain PUFAs (i.e., LA and ALA) were associated with reduced colorectal cancer risk, whereas longer-chain PUFAs (i.e., AA, EPA, and DPA) were associated with an increased colorectal cancer risk.Impact: The interaction of PUFAs with aspirin/NSAID use indicates a shared colorectal cancer inflammatory pathway. Future research should continue to improve PUFA genetic instruments to elucidate the independent effects of PUFAs on colorectal cancer.

Dataset Information

Omega-3 polyunsaturated fatty acids as adjuvant therapy of colorectal cancer.

Publications

Omega-3 polyunsaturated fatty acids as adjuvant therapy of colorectal cancer.

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